BLEEDING DISORDERS

SRUTHI PRIYADHARSHINY S
JR 1, PEDIATRIC AND PREVENTIVE DENTISTRY
TABLE OF CONTENTS
• Introduction • Fibrinolytic system
• Bleeding disorders • Hemorrhage
• Classification of bleeding disorders • Disorders of vessel abnormalities
• Platelets • Disorders of platelet
• Thrombopoiesis • Coagulation disorder
• Hemostasis • Tests for hemostasis
• The hemostatic balance • Dental management of patients
• Coagulation cascade with bleeding disorder
• Conclusion
INTRODUCTION
• Blood must be maintained in a fluid state in order to function as a transport system and
must also be able to solidify to form a clot following an injury.
• Bleeding is the escaping of blood from the circulatory system.
• Bleeding disorders constitute an important group of disorders in hematology.
BLEEDING DISORDERS
• Bleeding disorders or hemorrhagic diatheses are a group of disorders characterized by
defective hemostasis with abnormal bleeding.
• The tendency to bleed may be spontaneous in the form of small hemorrhages into the skin
and mucous membranes (e.g. petechiae, purpura, ecchymoses), or there may be excessive
external or internal bleeding following trivial trauma and surgical procedure (e.g.
haematoma, hemarthrosis etc).
• Bleeding disorders may be due to defects in primary haemostasis [platelet or vascular
disorders] or defects in secondary haemostasis [coagulation protein disorders].
• May be inherited due to genetic transmission or acquired secondary to diseases
 DISORDER OF
QUALITATIVE VESSEL WALL
ABNORMALITIES
DISORDERS QUANTITATIVE
OF DISORDERS OF
PLATELETS PLATELETS

BLEEDING
DISORDERS
COAGULATION FIBRINOLYTIC
DISORDERS DEFECTS
• DISORDERS OF VESSEL WALL
ABNORMALITIES
Hereditary Haemorrhagic Telangiectasia

Inherited Connective Tissue disorders

1. Ehlers-Danlos Syndrome
2. Marfan Syndrome
Acquired Connective Tissue disorders

1. Scurvy
2. Henoch Schonlein Purpura
3. Haemolytic Uremic Syndrome
4. Infection
5. Steroid Purpura
6. Senile Purpura
• QUALITATIVE DISORDERS OF • COAGULATION DISORDERS
PLATELET Congenital Coagulation disorders
Glanzmann Thrombasthenia
1. Haemophilia A and B
Bernard Soulier Syndrome
2. Von Willebrand disease
• QUANTITATIVE DISORDERS OF 3. Other factors deficiency
PLATELET
Acquired Coagulation Disorders
Thrombocytopenia
1. Liver disease
1. Immune thrombocytopenic purpura
2. Vitamin K deficiency
2. Thrombotic thrombocytopenic purpura
3. Disseminated Intravascular
3. Wiskott Aldrich Syndrome Coagulation
4. Heparin induced thrombocytopenia
Thrombocytosis
PLATELETS
• Platelets are small (1-4 mm in diameter), discoid, non-nucleate structures containing red-
purple granules.
• The normal platelet count ranges from 150,000-400,000/micro litre.
• The lifespan of platelets is 7-10 days.
• Factors such as stress, epinephrine and exercise stimulate platelet production.
THROMBOPOIESIS
• Platelets are formed in the bone marrow by a process of fragmentation of the cytoplasm
of megakaryocytes.
• Platelet production is under the control of thrombopoietin.
• The formation of platelets from the stem cell takes about 10 days.
The stages in platelet production are :
• The earliest precursor of
MEGAKARYOBLAST platelets in the bone marrow
• It arises from haematopoietic
stem cell

• In megakaryoblast
nuclear chromatin
replicates repeatedly
without cell division.
PROMEGAKARYOCYTE • This results in a large
cell containing up to
32 times the normal
diploid content of
nuclear DNA
 • A mature megakaryocyte is a
large cell, 30-90 μm in diameter,
and contains 4-16 nuclear lobes
MEGAKARYOCYTE having coarsely clumped
chromatin.
• The cytoplasm contains red-
purple granules.

• They are formed from

pseudopods of megakaryocyte
cytoplasm which get detached
PLATELETS into the blood stream.
• Each megakaryocyte may form up
to 4000 platelets.
 PRIMARY
HEMOSTASIS

HEMOSTASIS
SECONDARY
HEMOSTASIS
HEMOSTASIS
• Normal hemostasis comprises a series of regulated processes that maintain blood in a
fluid, clot-free state in normal vessels while rapidly forming a localized hemostatic plug at
the site of vascular injury.
• Vascular injury initially causes transient arteriolar constriction through reflex neurogenic
mechanisms, augmented by local secretion of endothelin.

After vascular injury, local neuro-humoral factors induce a transient vasoconstriction .

PRIMARY HEMOSTASIS
• It is an immediate phenomenon appearing within seconds of injury
• Endothelial injury exposes highly thrombogenic subendothelial extracellular matrix (ECM),
facilitating the initial platelet plug called primary hemostasis.

Platelets bind via glycoprotein 1b (GpIb) receptors to von Willebrand factor (vWF) on exposed extracellular matrix
(ECM) and are activated, undergoing a shape change and granule release. Released adenosine diphosphate (ADP)
and thromboxane A2 (TxA2) induce additional platelet aggregation through binding of platelet GpIIb-IIIa
receptors to fibrinogen. This platelet aggregate fills the vascular defect, forming the primary hemostatic plug.
 Platelet
• Platelets adhere to
collagen in the sub- release • This process is
endothelium. mediated by
• The adhesion to the • After adhesion, fibrinogen which
vessel wall is further platelets become forms bridge between
stabilized formation activated and release adjacent platelets via
of a link between von three types of glycoprotein
Willebrand factor and granules from their receptors on
another platelet cytoplasm: dense platelets, GpIIb-IIIa
receptor, GpIb-IX granules, α-granules complex.
complex and lysosomal
vesicles which release Platelet
Platelet certain products that
aids in platelet aggregation
adhesion aggregation.
Platelet adhesion and aggregation. Von Willebrand factor
functions as an adhesion bridge between subendothelial collagen and the
glycoprotein Ib (GpIb) platelet receptor. Platelet aggregation is accomplished
by fibrinogen binding to platelet GpIIb-IIIa receptors on different
platelets.
SECONDARY HEMOSTASIS
• This involves plasma coagulation system resulting in fibrin plug formation and takes several
minutes for completion.
• Activated thrombin promotes the formation of an insoluble fibrin clot which is also a potent
activator of additional platelets, which serve to reinforce the hemostatic plug. This is called
secondary hemostasis which results in the formation of a stable clot capable of preventing
further hemorrhage.

Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin
polymerization, “cementing” the platelets into a definitive secondary hemostatic plug that is larger and more
stable than the primary plug and contains entrapped red cells and leukocytes.
THE HEMOSTATIC BALANCE
• Endothelial cells are central regulators of hemostasis; the balance between the anti- and
prothrombotic activities of endothelium determines whether thrombus formation,
propagation,or dissolution occurs.
• Haemostasis is a complex process that involves interactions between blood vessel wall,
platelets and coagulation factors.
COAGULATION CASCADE
• Coagulation cascade consists of a cascade of soluble inactive zymogen proteins.
• When proteolytically cleaved and activated, each is capable of activating one or more
components of the coagulation cascade.
• The coagulation cascade ends by the formation of fibrin clot.
CLOTTING FACTORS
FIBRINOLYTIC SYSTEM
• Fibrinolysis is a process of dissolution of fibrin clot and thrombus by activating tissue
plasminogen activator released from endothelial cells.
• As bleeding is controlled, counterregulatory mechanisms [factors that produce
fibrinolysis] are set into motion to ensure that clot formation is limited to the site of injury.

Counterregulatory mechanisms, such as release of t-PA (tissue

plasminogen activator, a fibrinolytic product) and thrombomodulin
(interfering with the coagulation cascade), limit the hemostatic
process to the site of injury.
HAEMORRHAGE
DEFINITION
Hemorrhage is an acute loss of blood from a
damaged blood vessel.
• CLASSIFICATION OF HAEMORRHAGE
Depending on the source of bleeding:
External hemorrhage

When bleeding is revealed and seen outside. E.g. EPISTAXIS

Internal hemorrhage

Bleeding is concealed and is not seen outside. E.g. INTRA-CRANIAL

HEMATOMAS
Depending on the nature of bleeding vessel:
Arterial hemorrhage

Bright red in color and blood is emitted as a jet with each heartbeat.
Venous hemorrhage

Dark red in color and blood flow is steady.

Capillary hemorrhage

Bright red in color and generalized ooze of blood instead of blood flow.
Depending upon time of hemorrhage:
Primary hemorrhage

Occurs at the time of trauma or surgery.

Reactionary hemorrhage

Occurs within 24 hours of trauma or surgical procedure.

Secondary hemorrhage

Occurs after 7 to 14 days of trauma or surgical procedure.

Depending upon volume of blood loss
Mild haemorrhage: Blood loss less than or equal to 500 mL
Moderate haemorrhage: Blood loss 500-1000 mL
Severe haemorrhage: Blood loss more than or equal to 1000 mL
DISORDERS OF VESSEL
WALL ABNORMALITIES
 • Allergic
CAUSES purpura
• Drug induced
•
•
Bacterial
Viral
vascular • Rickettsia
purpura • Protozoal
• Purpura
fulminans

AUTOIMMUNE INFECTIONS

• Hereditary
hemorrhagic STRUCTURAL
telangiectasia MALFORMATI MISCELLANEOUS
• Hereditary ON
connective
tissue
disorders
• Acquired
connective
tissue
disorders
HEREDITARY HEMORRHAGIC
TELANGIECTASIA
• AD disorder that leads to vascular malformation.
• Also known as Osler Weber Rendu syndrome.
• Mucocutaneous condition characterized by arteriovenous malformation.
• ETIOPATHOGENESIS:
1. Mutations in at least FOUR genes can cause HHT.
2. The two major genes responsible are on chromosome 9 (mutation of ENG or endoglin
gene) which leads to HHT 1 and on chromosome 12 (mutation of activin receptor- like
kinase-1 ALK1-ACVRL1) which leads to HHT 2.
CLINICAL FEATURES

• One of the early signs of the disease is EPISTAXIS and BLEEDING FROM THE ORAL
CAVITY.
• Involvement of oral mucous membrane.
• Nasal and oropharyngeal mucosae exhibits numerous scattered red papules1 to 2 mm in
size.
• Spider-like telangiectasia is present.
• Associated with CREST syndrome.
• Systemic involvement is seen in the hands, neck, chest and feet, GI mucosa, genitourinary
tract and conjunctival mucosa.
 NASAL SPIDER PAPULES IN
EPISTAXIS TELANGIECTASIA ORAL MUCOSA

TELANGIECTASIA IN THE CREST SYNDROME [CUTANEOUS SYSTEMIC

PERI-UNGAL REGION SCLEROSIS ]
• Oral manifestation is seen in the vermillion zone of lips, tongue, buccal mucosa,
palate, floor of the mouth.
CURACAO CRITERIA FOR DIAGNOSIS OF HHT
• Since the most common immunological route for the entry of bacteria into the blood stream
is from the gingival mucosa, it is very important to inform the dentist before any dental
work, including dental cleaning.
• If pulmonary AVMs are present, the bacteria, once in the bloodstream, can pass through
them and may lodge in the brain and cause a brain abscess. A brain abscess is an extremely
serious medical emergency and could be life threatening. If an HHT patient has not been
specifically screened for lung AVMs, to prevent a brain abscess antibiotics must be taken
prior to any dental procedure
• It is essential that patients with HHT receive antibiotics before dental cleaning or dental
work of any kind (American Heart Association Guidelines).
• Furthermore, there are medications that should not be routinely prescribed for HHT patients.
Anti-inflammatory agents should generally not be taken by individuals with HHT because
these medications can increase bleeding. Often these medications are prescribed following
dental procedures.
INHERITED CONNECTIVE TISSUE
DISORDERS
1. EHLERS-DANLOS SYNDROME {Tenascin X
deficiency syndrome, lysyl hydroxylase deficiency}
• AD disorder
• It affects the skin, joints and blood vessel due to genetic defect in collagen synthesis.
• ETIOPATHOGENESIS:
1. The genes mutated in types I and II are COL5A1, COL1A1, Tenascin X genes.
2. In type IV decreased amount of type III collagen is seen.
3. In types V and VI deficiency of hydroxylase and lysyl oxidase is noted.
 • CLINICAL FEATURES:
i. Hyper elasticity of skin EASY BRUISING AND
ii. Hyperextensibility of joints DEFECTIVE HEALING
OF SKIN
iii. Fragility of the skin and blood vessels

HYPEREXTENSIBILITY HYPERELASTICITY
OF JOINTS OF SKIN
• ORAL MANIFESTATION
i. Gorlin sign: 50% of the patients can touch their nose with their tongue.
ii. Easy bruising and bleeding during minor manipulations of the oral mucosa.
iii. Hypermobility of the TMJ, repeated dislocation of the jaw.

GORLIN SIGN
• DIAGNOSTIC CRITERIA
1. Hess test
i. Also known as Rumpel-Leede Test
ii. It is used to assess capillary fragility.
iii. In this test pressure is applied to the forearm with a blood pressure cuff inflated to a
value between systolic and diastolic pressure for 10 minutes. After removing the cuff,
the number of petechiae appearing in 3 square cm area over the cubital fossa in the
next 5 minutes are counted.
iv. Presence of more than 20 petechiae is considered a positive test.
2. MARFAN SYNDROME
• AD disorder of the connective tissue characterized by loss of elastic tissue.
• ETIOPATHOGENESIS:
1. Caused by a variety of mutations in the FBN1 gene {Fibrillin 1}. This mutation causes
production of abnormal fibrillin protein leading to abnormalities in the elastic property of
connective tissue.
2. More recently TGF beta is implicated in the failure of normal elastic tissue formation.
• Marfan syndrome is classified as either type 1 or type 2. Type 1 is the most common presentation and
is caused by mutations in the gene FBN1, located on chromosome 15. Type 2 is less common and is
caused by a mutation in the gene that encodes transforming growth factor β receptors 1 and 2.
• CLINICAL
FEATURES:
An aneurysm of the aorta can cause severe complications in Marfan syndrome patient. It
causes the walls of the aorta to tear apart leading to massive bleeding.
For diagnosis of Marfan’s syndrome, major findings are required in two out of the three main
systems affected as well as involvement of a third organ system.
• Antibiotic prophylaxis should be used for oral procedures, such as
orthodontic banding, tooth extraction, and periodontal treatment.
• Oral administration of 50 mg/kg of amoxicillin (or 50 mg/kg of intravenous
or intramuscular ampicillin for children who are unable to take oral
medication) is recommended before surgery. Individuals who are allergic to
amoxicillin or ampicillin should take 50 mg/kg of cephalexin or 20 mg/kg of
clindamycin. Those patients who are allergic to amoxicillin or ampicillin and
unable to take oral medication should be administered intravenously
cefazolin/ ceftriaxone 50 mg/kg (intravenously or intramuscularly).
• For patients requiring tooth extraction for orthodontic purposes, the clinician
should consider an anesthetic containing felypressin, given that the use of
epinephrine may cause acceleration of cardiac function.
• Monitoring of blood pressure and aortic pulse wave velocity is strongly
recommended during oral surgery procedures for patients with Marfan
syndrome.
ACQUIRED CONNECTIVE TISSUE
DISORDER
1. SCURVY
• Vitamin C deficiency.
• Vitamin C also known as L-ascorbic acid is a water soluble vitamin.
• SOURCES: citrus fruits like amla, lemon, guava, orange.
• Highest tissue concentration of Vitamin C is found in pituitary and adrenal gland.
• DIETARY INTAKE:
According to National Health and Nutrition Examination Survey
1. Infants- 35 mg/day
2. Adults- 60 mg/day
• Scurvy occurs with a deficiency of less than 10mg/day
• Severe deficiency of vitamin C causes SCORBUTIC GINGIVITIS.
• ROLE OF VITAMIN C:
1. Collagen synthesis.
2. Vitamin C is a co-factor in many biological processes.
• CLINICAL SPECTRUM OF SCURVY:
• ORAL MANIFESTATION:
1. Interdental and marginal gingiva- swollen, bright red
2. In severe cases, gingiva is boggy, ulcerates and bleeds. Foul breath present.
3. Loss of bone and loosening of teeth

• LABORATORY FINDINGS:
1. Increased bleeding time
2. Abnormal capillary fragility test [Hess test]
2. HENOCH- SCHONLEIN PURPURA
• Henoch-Schonlein or anaphylactoid purpura is a self-limited type of hypersensitivity vasculitis
occurring in children and young adults.
• Circulating immune complexes are deposited in the vessel wall consisting of IgA, C3 and fibrin.
• The hypersensitivity vasculitis produces purpuric rash on the extensor surfaces of arms and
legs, as well as hematuria, colicky abdominal pain due to bleeding into the GIT, polyarthralgia
and acute nephritis.

3. HEMOLYTIC- URAEMIC SYNDROME

• Haemolytic-uraemic syndrome is a disease of infancy and early childhood in which there is
bleeding tendency and varying degree of acute renal failure.
• The disorder remains confined to the kidney where hyaline thrombi are seen in the glomerular
capillaries.
4. INFECTION
• Many infections cause vascular haemorrhages either by causing toxic damage to the
endothelium or by DIC.

5. DRUG REACTIONS
• Certain drugs form antibodies and produce hypersensitivity vasculitis responsible for
abnormal bleeding.

6. STEROID PURPURA
7. SENILE PURPURA
DISORDERS OF
PLATELET
 CLASSIFICATION OF PLATELET
DISORDERS
QUANTITATIVE QUALITATIVE
THROMBOCYTOPENIA THROMBOCYTOSIS CONGENITAL ACQUIRED

Idiopathic/ Immune Benign or reactive process Glanzmann’s Drug induced

thrombocytopenic purpura thrombasthenia

Thrombotic Myeloproliferative disorders Bernard-Soulier Acute or chronic

thrombocytopenic purpura syndrome leukemia

Storage granule Myelofibrosis

Wiskoff’s Aldrich syndrome abnormalities

Heparin induced Anemia

QUANTITATIVE
DISORDERS OF
PLATELET
THROMBOCYTOPENIA
• Thrombocytopenia is defined as a reduction in the peripheral blood platelet count below the lower
limit of normal i.e. below 150,000/ml.
• Thrombocytopenia is associated with abnormal bleeding that includes spontaneous skin purpura and
mucosal hemorrhages as well as prolonged bleeding after trauma.
• Spontaneous haemorrhagic tendency becomes clinically evident only after severe depletion of the
platelet count to level below 20,000/ml.
• Thrombocytopenia may result from 4 main groups of causes:
A. Impaired platelet production.
B. Accelerated platelet destruction.
C. Splenic sequestration.
D. Dilutional loss.
IMMUNE THROMBOCYTOPENIA
• Autoimmune disorder characterized by antibody-mediated platelet destruction and decreased
platelet production.

Opsonized platelets by autoantibodies are destroyed by macrophages in spleen and

peptide fragments expressed with MHC class II stimulate helper T cells, following
activation of autoreactive B cells. Impaired Tregs fail to suppress this vicious cycle.
Autoantibodies also suppress megakaryocytopoiesis. Autoreactive cytotoxic T cells
may play a role in the destruction of platelets and megakaryocytes.
• On the basis of duration of illness, ITP is classified into acute and chronic forms, both of
which have different pathogenesis:
ACUTE
Self- limited
Seen in children
Viral infections {HCV, HIV, CMV, Infectious
mononucleosis}
Formation of immune complexes containing viral
antigens, and by formation of antibodies against
viral antigens which cross react with platelets and
lead to their immunologic destruction.
Spontaneous resolution in 2 to 6 months
CHRONIC
Common
Adults {especially women of child bearing age, 20 to
40 years}
Unknown etiology
Formation of anti-platelet autoantibodies which are
directed against target antigens on the platelet
glycoproteins, Gp IIb-IIIa and Gp Ib-IX complex
which also interfere in their function. Sensitised
platelets are destroyed mainly in the spleen
Longer than 6 months
• CLINICAL FEATURES:
1. Spontaneous purpuric or hemorrhagic rash [petechiae to ecchymosis].
2. Epistaxis
3. Hematuria
4. Hematemesis
5. Menorrhagia
6. Intra cranial hemorrhage is a serious but rare complication
• ORAL MANIFESTATIONS
1. Severe and profuse gingival bleeding
2. Petechiae on the palate
3. Contraindicates many surgical procedures
• LABORATORY FINDINGS:
1. Platelet count in a range of 10000-50000 platelets per cu.mm.
2. Prolonged bleeding time
3. Hess test is strongly positive
• MANAGEMENT:
THROMBOTIC THROMBOCYTOPENIC PURPURA

• Uncommon, life threatening multi-system disorder.

• Thrombotic thrombocytopenic purpura (TTP) and hemolytic- uremic syndrome (HUS) are a group of
thrombotic microangiopathies which are essentially characterized by triad of thrombocytopenia,
microangiopathic haemolytic anaemia and formation of hyaline fibrin microthrombi within the
microvasculature throughout the body.
• The intravascular microthrombi are composed predominantly of platelets and fibrin. The widespread
presence of these platelet microthrombi is responsible for thrombocytopenia due to increased
consumption of platelets
• ETIOPATHOLOGY:
1. Deficiency of a protease enzyme ADAMTS13.

ITTP is primarily caused by severe deficiency of ADAMTS13, a plasma metalloprotease that cleaves von
Willebrand factor (VWF), resulting from acquired autoantibodies against ADAMTS13. The antibodies bind and
inhibit plasma ADAMTS13 activity, which hinders the cleavage of VWF, resulting in heightened platelet adhesion
and aggregation
ADAMTS13 is important in the cleavage in the A2 region
of VWF as it is secreted from endothelial cells. This
physiological action generates more active VWF
multimers. VWF multimers bind with platelets and this
action is important in primary hemostasis.
In TTP, the lack of ADAMTS13 generates an
increase in ultra large VWF multimers that
promote increased platelet binding and
aggregation. These break off as microthrombi
and result in organ damage
HUS is distinguished from TTP by absence of neurological symptoms, acute renal failure and
occurrence in children.
• DIAGNOSIS
Established by examination of biopsy (e.g. from gingiva) which demonstrates typical
microthrombi in arterioles, capillaries and venules, unassociated with any inflammatory
changes in the vessel wall.
HEPARIN INDUCED THROMBOCYTOPENIA
• The underlying mechanism of heparin-induced thrombocytopenia is formation of
antibody against platelet factor 4 (PF-4)-heparin complex. This specific antibody activates
the endothelial cells and initiates thrombus formation.
• Diagnosis is made by a combination of laboratory and clinical features with 4 Ts:
1. Thrombocytopenia
2. Thrombosis
3. Time of fall of platelet count
4. Absence of other causes of Thrombocytopenia.
WISKOTT-ALDRICH SYNDROME
• X-linked recessive condition in which there is a severe congenital IgM deficiency
• Defect in a protein called Wiskott-Aldrich syndrome protein [WASp].
• CLINICAL FEATURES:
1. Thrombocytopenic purpura
2. Eczema
3. Increased susceptibility to infection due to cellular and humoral immunodeficiency.
4. Early signs include petechiae, purpuric rash, ecchymoses.
5. Patients unable to produce antibodies against polysaccharide containing microbes like
pneumococci, H influenza, coliform bacilli.
• ORAL MANIFESTATION:
1. Spontaneous gingival bleeding
2. Palatal petechiae
• LABORATORY FINDINGS:
1. Reduced platelet count
2. Prolonged bleeding time
• TREATMENT:
1. Platelet transfusions
2. Bone marrow transplantation
3. Transfer factor
4. Rituximab
THROMBOCYTOSIS
• Thrombocytosis is defined as platelet count in excess of 4,00,000/ml.

• Thrombocytosis causes bleeding or thrombosis

• CLINICAL FEATURES
1. Bleeding tendency
2. Epistaxis
3. Bleeding into GIT, genito-urinary tract, CNS
4. Hemorrhage into skin
• ORAL MANIFESTATION
1. Spontaneous gingival bleeding
2. Prolonged bleeding after dental extractions.
QUALITATIVE
DISORDERS OF
PLATELET
GLANZMANN THROMBASTHENIA
• Autosomal recessive, hereditary chronic hemorrhagic disorder
• Defective platelet aggregation due to mutation in the gene for glycoprotein IIb/IIIa.
• CLINICAL FEATURES:
1. Spontaneous bleeding
2. Epistaxis
3. GIT bleeding
4. Hemarthrosis
5. Menorrhagia
• ORAL MANIFESTATION
1. Spontaneous gingival bleeding
2. Palatal petechiae
• LABORATORY FINDINGS
1. Prolonged bleeding time
2. Clot retraction is impaired
• TREATMENT
1. Microfibrillar collagen preparation with fibrinolytic inhibitors
2. Recombinant factor VIIa
BERNARD-SOULIER SYNDROME
• Rare disease of unknown etiology characterized by qualitative platelet defect.
• There is abnormality in genes for the glycoprotein gpIb leading to defect in platelet
adhesion.
• CLINICAL FEATURES
1. Spontaneous ecchymosis
2. Epistaxis
3. Bleeding into GIT
• ORAL MANIFESTATION
1. Gingival bleeding
2. Mucosal ecchymoses
• LABORATORY FINDINGS
1. Prolonged bleeding and clotting time
2. Normal platelet count
• TREATMENT:
1. Blood transfusion
COAGULATION
DISORDERS
CONGENITAL ACQUIRED

Hemophilia A and B Liver disease

Von Willebrand disease Vitamin K deficiency

Other factor deficiency DIC

ACQUIRED COAGULATION
DISORDERS
LIVER DISEASE
• Liver plays a major role in the clotting process.
• Site for synthesis of clotting factors and their inhibitors.
• Liver disease causes impaired hemostatic function.
• Most common findings in liver disease is THROMBOCYTOPENIA.
• CLINICAL FINDINGS
1. GI hemorrhage
2. No abnormal bleeding
3. Epistaxis
• ORAL MANIFESTATION
1. Recurrent ecchymosis
2. Severe generalized bleeding
• LABORATORY FINDINGS:
1. Decreased platelet count
2. Increased levels of PT and aPTT
• TREATMENT
1. Fresh frozen plasma
2. Cryoprecipitate
3. Recombinant factor VIIa
4. Thrombopoietin
VITAMIN K DEFICIENCY

• Causes Hemorrhagic disease of the newborn. Now uncommon due to the administration
of vitamin K at birth.
• Vitamin K is a fat soluble vitamin involved in both intrinsic and extrinsic pathway.
• ROLE OF VITAMIN K: Necessary for post-translational carboxylation of glutamate
which is necessary for calcium binding to proteins like prothrombin, factor II, VII, IX, X.
• SOURCE: Green leafy vegetables, liver, milk, vegetable oil.
• REQUIREMENT: 1-2 mcg/kg
• CLINICAL FEATURES:
1. Bleeding is severe
2. Melena
3. Large cephalohematoma
4. Bleeding from umbilical stump
• ORAL MANIFESTATION:
1. Gingival bleeding
2. PT levels <35%- bleeding immediately after tooth brushing
3. PT levels <20%- spontaneous gingival hemorrhage
• LABORATORY FINDINGS:
1. Increased PT and aPTT
• TREATMENT:
1. Vitamin K1 [0.5-1.0 mg IM]
2. Transfusion of plasma
DISSEMINATED INTRA-VASCULAR COAGULATION
• DIC is an acquired syndrome characterized by the systemic activation of coagulation and
results in the formation of thrombi throughout the microcirculation
• As a consequence, platelets and coagulation factors are consumed and, secondarily,
fibrinolysis is activated.
• DIC can give rise to either tissue hypoxia and microinfarcts caused by
microthrombi or to a bleeding disorder related to pathologic activation of
fibrinolysis and the depletion of the elements required for haemostasis and so it is
also known as CONSUMPTION COAGULOPATHY.
• PATHOPHYSIOLOGY

• DIC has two consequences.

• First, there is widespread fibrin deposition within the microcirculation. The
associated obstruction leads to ischemia in the vulnerable organs and hemolysis as
red cells are traumatized while passing through vessels narrowed by fibrin thrombi
(microangiopathic hemolytic anemia).
• Second, a bleeding diathesis results from the depletion of platelets and clotting
factors and the secondary release of plasminogen activators. Plasmin cleaves not
only fibrin (fibrinolysis) but also factors V and VIII, thereby reducing their
concentration further.
• In addition, fibrinolysis creates fibrin degradation products. These inhibit platelet
aggregation, have antithrombin activity, and impair fibrin polymerization, all of
which contribute to the haemostatic failure.
CLINICAL FEATURES
• Acute DIC (that associated with obstetric complications) is dominated by a bleeding diathesis,
• Chronic DIC (as seen in those with cancer) tends to manifest with signs and symptoms related to
thrombosis.

ACUTE CHRONIC
Generalized ecchymosis Extensive ecchymosis of extremities
Petechiae Without petechiae
Bleeding from previous venipuncture site
Hemorrhagic skin lesion Renal impairment
Neurological symptoms
Geographic acral cyanosis Trousseau sign
Epistaxis Recurrent episodes of epistaxis
GI bleeding Serious internal mucosal bleeding
Pulmonary hemorrhage Thrombosis
Hematuria
• LABORATORY FINDINGS
1. Prolonged PT and aPTT
2. Platelet count less than 50000/ cu.mm
3. Increased fibrin degradation products
• TREATMENT
• Acute DIC can be life-threatening and must be treated aggressively with
anticoagulants such as heparin or the coagulants contained in fresh frozen plasma.
• Conversely, chronic DIC is sometimes identified unexpectedly by laboratory
testing. In either circumstance, definitive treatment must be directed at the
underlying cause.
1. Anti-coagulants
2. Fresh frozen plasma
•CONGENITAL COAGULATION
DISORDERS
HEMOPHILIA
• Also known as Bleeder’s disease, disease of Hapsburg
• Hereditary disorder
• Defect carried by X chromosome and transmitted as a gender linked Mendelian recessive
trait.
• Broadly classified into:
Hemophilia A/ Classic hemophilia

Hemophilia B/ Christmas disease

Hemophilia C/ Rosenthal syndrome

Genetics

Hemophilia A Hemophilia B Hemophilia C

Genetic abnormalities
include deletions,
abnormalities with stop
codons, frame shift defects in
the gene responsible for
factor VIII production.
Partial and total deletions,
missense mutations result in
decrease or absence of factor
IX
Mutations of factor XI causes
failure, reduced production of
active protein and rarely
production of abnormal
molecule

• Genes for factor VIII and factor IX are located on the long arm of the X
chromosome in bands q28 and q27.
• Genes for factor XI located on chromosome 4.
HEMOPHILIA-A

• 80-85% hemophiliacs suffer from Hemophilia A.

• Occurs due to deficiency of factor VIII.
• X-linked recessive disorder in which females are carriers and affects males
• Affects every 1 in 10000 patients.
• Positive family history present
• Pedigree chart
Structure and function of factor VIII- vWF complex. Factor VIII and vWF circulates as a complex. vWF is also
present in the sub-endothelial matrix of normal blood vessels. Factor VIII takes part in the coagulation cascade by
activating factor X by means of factor IX. vWF causes adhesion of platelets to the sun-endothelial collagen
primarily through Gp1b platelet receptor.
HEMOPHILIA B

• Also called as Christmas disease.

• X- linked recessive disorder seen in 14% of the patients.
• CLINICAL FEATURES
1. Persistent bleeding, either spontaneous or following slight trauma.
2. Hemorrhage into subcutaneous tissues, internal organs and joints is a common feature.
3. Usually present from birth but becomes clinically apparent after several years.
• ISTH criteria classification of hemophilia
• ORAL MANIFESTATION:
1. Hemorrhage from any site in the oral cavity is a common finding.
2. Gingival hemorrhage may be massive and prolonged.
3. Tooth eruption and exfoliation shows severe prolonged haemorrhage.
4. Mandibular pseudotumor reported by Stoneman and Beirl- a condition in which there is
sub-periosteal bleeding with reactive new bone formation causing tumor like expansion
of bone.

Mandibular Pseudotumor
removed by ethanol
embolization
• LAB FINDINGS:
1. Prolonged coagulation time
2. BT is normal
3. PT and platelet aggregation is normal
4. aPTT is prolonged
• TREATMENT
1. Pre-operative transfusion of whole blood
2. Administration of factor VIII and factor IX concentrates respectively by IV
infusion
DENTAL MANAGEMENT
• PRE-OPERATIVE:
1. Consult the hematologist
2. Mild to moderate cases can be usually treated in the dental clinic whereas severe cases
should be treated in the hospital.
3. Replacement of factors VIII & IX one hour before the procedure.
4. Treat the acute infections with antibiotics.
5. Good surgical techniques, pressure packs, gel foam with thrombin to control bleeding.
6. It is essential to prevent accidental damage to the oral mucosa when carrying out any
procedure in the mouth.
7. Injury can be avoided by
 Careful use of saliva ejectors

 Careful removal of impressions

 Care in the placement of X-Ray films

• DURING DENTAL PROCEDURES
1. Block anaesthesia, lingual infiltration, and IM injections should be avoided.
2. Infiltration anaesthesia and intra-ligamentary injection usually given without any factor
replacement.
3. Orthodontic treatment, root canal without over instrumentation, polishing can be done.
4. Periodontal surgery, root planing, extraction, dento-alveolar surgery and complex oral
surgical procedures need factor replacement.
• POST-OPERATIVE:
1. In dental clinic, severe cases need second dose of factors VIII & IX.
2. Hospitalized patients will need additional doses of factor replacement. Also signs of
allergy should be checked periodically.
3. Avoid aspirin, aspirin containing compounds and other NSAIDs. Acetaminophen with or
without codeine is suggested for most patients.

GUIDELINES FOR DENTAL TREATMENT OF PATIENTS WITH INHERITED BLEEDING

DISORDERS Andrew Brewer, Oral& Maxillofacial Surgery on behalf of World Federation of
Hemophilia Dental Committee
VON WILLEBRAND’S DISEASE
• Also known as pseudo hemophilia.
• Autosomal dominant hereditary disorder.
• Manifested in both males and females.
• Characterized by prolonged bleeding time.
CLASSIFICATION OF vWD

• TYPE I: Characterized by a partial quantitative decrease of normal vWF and factor VIII.
• TYPE II: vWD is a variant of the disease with primarily qualitative defects of vWF. It is
either autosomal dominant or recessive.
• TYPE III: Most severe and rarest form of vWD, characterized by marked deficiency of
both vWF and factor VIII.
CLINICAL FEATURES
1. Prevalence rate is 0.9-1.3%.
2. Many children are asymptomatic and rarely diagnosed as a result of positive family
history.
3. Excessive bleeding commonly seen in nose, skin, gingiva.
• ORAL MANIFESTATIONS
1. Gingival bleeding in 39% cases.
2. In some instances there is spontaneous bleeding and other cases bleeding occurs as a
result of brushing.
LABORATORY FINDINGS
• Increased BT
• PT, CT, aPTT are normal.
• Positive torniquet test in 50% cases.

TREATMENT
• Transfusion of plasma and/or anti-hemophilic factor.
• Desmopressin.
• Use of cryoprecipitate
• Antifibrinolytic agents
• Local hemostatic agents.
Stubbs M LloydJ. A protocol for the dental management of von Willebrand’s
disease, hemophilia A and hemophilia B. Australian dental journal. 2001 March; 46
(1):37-40.
DISEASE DEFICIENCY ROLE

Para-hemophilia Factor V [proaccelerin] Conversion of pro-thrombin to

thrombin

Afibrinogenemia/ Fibrinogen Helps in blood clotting

Hypofibrinogenemia
FIBRIN STABILIZING FACTOR
DEFICIENCY
• Autosomal recessive disorder
• Mutations seen in gene encoding the catalyst alpha subunit located on chromosome 6.
• Activated factor XIII cross links fibrin or stabilizes it by transamination.
• CLINICAL FEATURES
1. Severe post-surgical bleeding episodes
2. Hemarthrosis
3. Defective wound healing
4. Bleeding from the stump of umbilical cord within first day to weeks of life [seen in 80%]
• ORAL MANIFESTATION:
1. Bleeding from mouth and gums during teething.
• LABORATORY FINDINGS
Measurement of clot stability- commonly used screening test [clot solubility test]

The principle here is that the clot formed in the presence of factor XIII and Ca ions are stable
for at least an hour in 1% monochloracetic acid solution and in 5 mol/litre urea, whereas
clots formed in the absence of factor XIII dissolve rapidly
Factor XIII alpha and factor XIII beta antigen levels by means of ELISA techniques

• TREATMENT
1. Plasma, cryoprecipitate and factor XIII concentrate.
TESTS FOR HEMOSTASIS
• In order to establish a definite diagnosis in any case suspected to have abnormal
hemostatic functions, the following scheme is followed:
1. Comprehensive clinical evaluation, including the patient’s history, family history and
details of the site, frequency and character of haemostatic defect.
2. Series of screening tests for assessing the abnormalities in various components involved
in maintaining hemostatic balance.
3. Specific tests to pinpoint the cause.
INVESTIGATION OF DISORDERED
VASCULAR HEMOSTASIS
Disorders of vascular hemostasis may be due to increased vascular permeability, reduced
capillary strength and failure to contract after injury. Tests of defective vascular function are
as under:
1. BLEEDING TIME:
• This simple test is based on the principle of formation of hemostatic plug following a
standard incision on the volar surface of the forearm.
• The time the incision takes to stop bleeding is measured.
• The test is dependent upon capillary function as well as on platelet number and ability of
platelets to adhere to form aggregates.
• Normal range is 3-8 minutes.
• A prolonged bleeding time may be due to following causes:
i. Thrombocytopenia.
ii. Disorders of platelet function.
iii. von Willebrand’s disease.
iv. Vascular abnormalities (e.g. in Ehlers-Danlos syndrome).
v. Severe deficiency of factor V and XI.
2. HESS TEST
• Also known as Rumpel-Leede Test
• It is used to assess capillary fragility.
• In this test pressure is applied to the forearm with a blood pressure cuff inflated to a value
between systolic and diastolic pressure for 10 minutes. After removing the cuff, the
number of petechiae appearing in 3 square cm area over the cubital fossa in the next 5
minutes are counted.
• Presence of more than 20 petechiae is considered a positive test.
• The test is positive in increased capillary fragility as well as in thrombocytopenia.
INVESTIGATION OF PLATELETS AND
PLATELET FUNCTION
Hemostatic disorders are commonly due to abnormalities in platelet number, morphology
or function.
1. SCREENING TESTS:
The screening tests carried out for assessing platelet-related causes are as under:
i. Peripheral blood platelet count.
ii. Skin bleeding time.
iii. Examination of fresh blood film to see the morphologic abnormalities of platelets.
2. SPECIAL TESTS:
If these screening tests suggest a disorder of platelet function, the following platelet
function tests may be carried out:
i. Platelet adhesion tests such as retention in a glass bead column, and other
sophisticated techniques.
ii. Aggregation tests which are turbidometric techniques using ADP, collagen or
ristocetin.
iii. Granular content of the platelets and their release can be assessed by electron
microscopy or by measuring the substances released.
iv. Platelet coagulant activity is measured indirectly by prothrombin consumption index.
INVESTIGATIONS OF BLOOD
COAGULATION
• The normal blood coagulation system consists of cascade of activation of 12 coagulation
factors.
• These form intrinsic, extrinsic and common pathways which culminate in formation of
thrombin that acts on fibrinogen to produce fibrin.
• Fibrin clot so formed is strengthened by factor XIII which itself gets activated by thrombin.

1. SCREENING TESTS
2. SPECIAL TESTS
1. SCREENING TESTS:
• Whole blood coagulation time:
 The estimation of whole blood coagulation time done by various capillary and tube
methods is of limited value since it is an insensitive and non-specific test.
 Normal range is 4-9 minutes at 37°C.
• Activated partial thromboplastin time (APTT) or partial thromboplastin
time with kaolin (PTTK):
 This test is used to measure the intrinsic system factors (VIII, IX, XI and XII) as well as
factors common factors (factors X, V, prothrombin and fibrinogen).
 The test consists of addition of 3 substances to the plasma—calcium, phospholipid and a
surface activator such as kaolin.
 The normal range is 30-40 seconds.

 Prolonged PTTK (or APTT) is seen in:

i) Parenteral administration of heparin.

ii) Disseminated intravascular coagulation.
iii) Liver disease.
iv) Circulating anticoagulants.
• One-stage prothrombin time (PT):
 PT measures the extrinsic system factor VII as well as factors in the common pathway.

 In this, tissue thromboplastin (e.g. brain extract) and calcium are added to the test
specimen.
 The normal PT is 10-14 seconds.

 The common causes of prolonged one-stage PT are as under:

i) Administration of oral anticoagulant drugs.

ii) Liver disease, especially obstructive liver disease.
iii) Vitamin K deficiency.
iv) Disseminated intravascular coagulation.
• Measurement of fibrinogen:
 The SCREENING TESTS for fibrinogen deficiency are semiquantitative fibrinogen titre
and thrombin time (TT).
 The normal value of thrombin time is under 20 seconds.

 Following are the common causes for higher values in both these tests:

• i) Hypofibrinogenaemia (e.g. in DIC).

• ii) Raised concentration of FDP.
• iii) Presence of heparin.
2. SPECIAL TESTS:
• Coagulation factor assays:
 These bioassays are based on results of PTTK or PT tests and employ the use of substrate
plasma that contains all other coagulation factors except the one to be measured.
 The unknown level of the factor activity is compared with a standard control plasma with a
known level of activity.
 Results are expressed as percentage of normal activity.

• Quantitative assays:
 The coagulation factors can be quantitatively assayed by immunological and other
chemical methods.
INVESTIGATIONS OF FIBRINOLYTIC
SYSTEM
• Increased levels of circulating plasminogen activator are present in patients with
hyperfibrinolysis.
• SCREENING TESTS:
1. Estimation of fibrinogen.
2. Fibrin degradation products (FDP) in the serum.
3. Ethanol gelation test.
4. Euglobin or whole blood lysis time.
• SPECIFIC TESTS:
1. Functional assays
2. Immunological assays by ELISA
3. Chromogenic assays of plasminogen activators, plasminogen, plasminogen activator
inhibitor, and FDP.
DISTINGUISHING FEATURES BETWEEN
DISORDERS OF PLATELETS, VESSEL
WALL AND COAGULATION.
FINDINGS DISORDERS OF DISORDERS OF
PLATELET OR VESSEL COAGULATION
PETECHIAE Characteristic Rare
DEEP DISSECTING Rare Characteristic
HEMATOMA
HEMARTHROSIS Rare Characteristic
DELAYED BLEEDING Rare Common
BLEEDING FROM Profuse Minimal
SUPERFICIAL CUT AND
SCRATCHES
POSITIVE FAMILY HISTORY Rare Common

SEX OF THE PATIENT Relatively more common in 80-90% males

females
DENTAL MANAGEMENT
OF PATIENTS WITH
BLEEDING DISORDER
IDENTIFICATION OF PATIENT WITH BLEEDING
DISORDER
• Begin with thorough medical history. Patient reports of family history of bleeding
disorders may help to identify the inherited disorders
• A patient’s past dental history of bleeding during surgery, extractions
• Identification of medications such as anti-coagulants, heparin, aspirin, NSAIDs, cytotoxic
chemotherapy is essential.
LOCAL HAEMOSTATIC MECHANISM OF ACTION
AGENTS
GELFOAM Absorbable gelatin sponge
material which provides a stable
scaffold for clot formation.
SURGICEL Oxidized regenerated cellulose,
exerts physical effect rather than
physiological.
BLEED-X Hemostatic product containing
microporous polysaccharide that
dehydrates blood and
accelerates clotting.
TISSEEL Fibrin sealant, adhesive action
that bonds fibrin to the clot,
CYKLOKAPRON Used in the form of a
[TRANEXAMIX ACID] mouthwash after surgical
procedures to inhibit post-
operative bleeding as a 4.8%
aqueous solution.
PRECAUTIONS
Should not be used under
epithelial incisions or flaps as it
inhibits healing.
Can be used safely.
Can be used safely.
Technique sensitive as it requires
special attention for preparation
and is reserved for complex
procedures.
To be used carefully in children.
Swallowing the mouthwash may
result in increased serum levels
than required.
ORAL SURGICAL PROCEDURES

• Pre-operative factor levels of at least 40-50% of normal activity have been obtained by
transfusion.
• Surgical bleeding due to fibrinolysis controlled by

ANTI- • Epsilon-aminocaproic acid

• Tranexamic acid
FIBRINOLYTICS
• Pressure gauge
•
LOCAL •
Sutures
Vasoconstrictors
MEASURES • Surgical stent
• Topical thrombin
• EACA is systemic therapy that can be given orally or IV until bleeding stops [75mg/kg every
6 hours]
• Tranexamic acid as 4.8% oral rinse was found to be 10 times more effective than EACA in
preventing post-extraction bleeding
• Local measures have no direct effect on hemostasis, protects clot from masticatory
trauma.
• Topical thrombin is applied on extraction site in non-acidic medium on oxidized
cellulose . Surgi-foam is an absorbable gelatin sponge with intrinsic hemostatic
properties.
• Diet restriction to full liquids for 24-48 hours, reducing the amount of chewing.
RESTORATIVE AND PROSTHODONTIC THERAPY
• RESTORATIVE PROCEDURES:
1. Rubber dam isolation is advised to
minimize the risk of lacerating the soft
tissue in the operative field and to
avoid creating ecchymosis.
• PROSTHODONTIC THERAPY:
1. Dental trauma should be minimized by
prompt and careful post-insertion
adjustment.

2. Matrices, wedges and gingival

retraction cord should be used
cautiously to protect soft tissue and
improve the visibility.
• PAIN CONTROL:
1. Intra-pulpal anesthesia is safe and effective following access for pulpal extirpation.
Intra-muscular injection is contraindicated.
2. If a hematoma develops, ice packs should be applied to the area to stimulate
vasoconstriction.
3. Intra-venous sedation with diazepam and nitrous oxide analgesia used as adjunct to
control anxiety and remove the need for LA. The use of NSAIDs and aspirin is
contraindicated for pain management.
• ENDODONTIC THERAPY:
1. Generally there are no contraindications in root canal therapy but instrumentations
should not extend beyond the apex. Filling beyond the apical seal should be avoided.
2. Intra-pulpal application of epinephrine to the apical area is usually successful in
providing hemostasis.
ORTHODONTIC THERAPY
• Bleeding due to minor cuts responds to gauze pressure
• Fixed orthodontic appliance must be preferred over removable functional appliance for
the patient with high risk of bleeding
PATIENTS ON ANTI-COAGULANTS

• Management of the dental patient on anti-coagulant therapy involves consideration of the

degree of anti-coagulation achieved as gauzed by PT/INR, the dental procedure planned
and the level of thromboembolic risk for the patient.
• For surgical procedures, physician consultation is advised. Coumarin withdrawal is
necessary 2 days prior to surgery in order to return the patient’s INR.
• High risk cardiac patients undergoing high bleeding risk surgical procedures should be
managed with combination unfractioned heparin-coumarin method.
• Use of anti-fibrinolytics alleviate the need to reduce the oral-anticoagulants
PERIODONTAL THERAPY

• Periodontal health is of importance for hemophiliac patients for two important reasons:
1. Hyperemic gingiva contributes to spontaneous bleeding in the gingiva.
2. Periodontitis is the leading cause for tooth morbidity, necessitating extraction

Periodontal
Bleeding disorder
Careful sub- surgical
patients are
gingival scaling procedures
prone to oral
with fine scalers warrant elevating
hygiene neglect
rarely warrants circulating factor
due to tooth
replacement levels to 50% and
brush induced
therapy. use of anti-
bleeding.
fibrinolytics.
• Severely inflamed and swollen oral tissues are best treated by rinses of chlorhexidine or
gross debridement with hand instruments to allow gingival shrinkage before deep scaling.
• Deep gingival scaling and root planing should be performed quadrant by quadrant to
reduce gingival area exposed to bleeding
• Periodontal packing aids hemostasis and protects the surgical site.
CONCLUSION
• Bleeding disorders constitute an important class of diseases which should
be managed appropriately.
• Laboratory diagnosis in a systemic manner is very important to reach a
correct diagnosis.
• A thorough understanding and knowledge about bleeding disorders is very
much needed for dental professionals to minimize the complications of
many treatment procedures
THANK YOU